UCL School of Pharmacy, London, UK.
Innovenn UK Ltd., Sand Hutton, York, UK.
Int J Cosmet Sci. 2021 Feb;43(1):107-112. doi: 10.1111/ics.12675. Epub 2020 Dec 25.
The safety assessment of personal care products often entails determining dermal absorption of their ingredients. Such experiments are typically performed in human or animal skin in vitro; however, ethical and safety considerations are associated with obtaining these tissues. Several human skin equivalent models (HSEs) have been developed as alternatives to human tissue. The barrier function of such models however, is normally less developed than human skin. Here, we examine the permeability of the HSE LabSkin to a model compound, 3-O-ethyl-l-ascorbic acid (EA) compared with human skin.
Skin uptake and permeation of EA was investigated in vitro using heat-separated human epidermis and LabSkin . Finite dose (5 μL cm ) Franz-diffusion studies were conducted using 2 % (w/w) EA in a ternary solvent mixture comprising propylene glycol (PG), propylene glycol monolaurate (PGML), and isopropyl myristate (IPM). These excipients are commonly used in cosmetic products and they have been reported to promote permeation of EA in a different model, namely porcine skin.
Permeation of EA through LabSkin was evident from 2 h; however, EA permeation in human skin was not detected until 5 h. Similar amounts of EA permeated through the two membranes at time points 8, 10, 12 and 24 h (p > 0.05). The cumulative amounts of EA delivered through LabSkin at 24 h were 41.3 ± 2.0 µg cm , corresponding to 55.1 ± 1.8 % of the applied dose. Similar amounts permeated across human skin, 49.4 ± 4.1 µg cm , accounting for 58.0 ± 4.2 % of the dose applied (p > 0.05).
The permeation of EA in LabSkin compared well with results for human epidermis in terms of the permeation profiles and the cumulative amounts of EA that permeated. The data suggest that the skin barrier of the two models was similar with regard to their overall permeability to the hydrophilic active EA. The findings are promising for the use of LabSkin as a surrogate for human skin in permeability testing. Future studies will focus on exploring the reproducibility and robustness of LabSkin for delivery of other actives that span a range of physicochemical properties.
个人护理产品的安全性评估通常需要确定其成分的经皮吸收。此类实验通常在人体或动物皮肤的体外进行；然而，获得这些组织与伦理和安全考虑有关。已经开发了几种人体皮肤等效模型（HSE）作为人体组织的替代品。然而，这些模型的屏障功能通常不如人体皮肤发达。在这里，我们研究了 HSE LabSkin 对模型化合物 3-O-乙基-L-抗坏血酸（EA）的通透性，与人体皮肤进行了比较。
使用热分离的人体表皮和 LabSkin ，在体外研究了 EA 的皮肤摄取和渗透。使用包含丙二醇（PG）、丙二醇单月桂酸酯（PGML）和肉豆蔻酸异丙酯（IPM）的三元溶剂混合物中的 2%（w/w）EA 进行有限剂量（5μL cm ）Franz 扩散研究。这些赋形剂常用于化妆品产品中，据报道它们可以促进不同模型（即猪皮）中 EA 的渗透。
从 2 小时开始，可以看出 EA 通过 LabSkin 的渗透；然而，直到 5 小时才检测到 EA 在人体皮肤中的渗透。在 8、10、12 和 24 小时的时间点，两种膜中渗透的 EA 量相似（p > 0.05）。在 24 小时内通过 LabSkin 传递的 EA 累积量为 41.3±2.0µg cm ，相当于应用剂量的 55.1±1.8%。通过人体皮肤渗透的量相似，为 49.4±4.1µg cm ，占应用剂量的 58.0±4.2%（p > 0.05）。
EA 在 LabSkin 中的渗透与人体表皮的渗透情况相当，无论是在渗透曲线还是渗透的 EA 累积量方面。数据表明，两种模型的皮肤屏障在整体对亲水性活性 EA 的渗透性方面相似。这些发现对于将 LabSkin 用作透皮测试中人体皮肤的替代品是有希望的。未来的研究将集中于探索 LabSkin 对跨越一系列物理化学性质的其他活性剂的输送的重现性和稳健性。
